期刊
PLOS PATHOGENS
卷 12, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1005805
关键词
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资金
- National Institutes of Health [AI076066, P30 AI045008]
- National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology [AI067854]
- Fonds de la Recherche Quebec-Sante (FRQ-S): Reseau SIDA/Maladies infectieuses
- Canadian Institutes of Health Research [MOP 103230, CTN 257]
- Canadian HIV Cure Enterprise Team Grant from the CIHR [HIG-133050]
- CANFAR
- Medical Research Council [MR/K012037/1] Funding Source: researchfish
- MRC [MR/K012037/1] Funding Source: UKRI
The loss of HIV-specific CD8(+) T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8(+) T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8(+) T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin(+) CD8(+) T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8(+) T cells differentiated HIV-specific from bulk memory CD8(+) T cell effector expansion. As infection progressed expression of perforin was maintained in HIV-specific CD8(+) T cells with high levels of T-bet, but not necessarily in the population of T-betLo HIV-specific CD8(+) T cells that expand as infection progresses. Together, these data demonstrate that while HIV-specific CD8(+) T cells in acute HIV infection initially possess cytolytic potential, progressive transcriptional dysregulation leads to the reduced CD8(+) T cell perforin expression characteristic of chronic HIV infection.
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